論文 - 詳細
| RRC ID | 6512 |
|---|---|
| 著者 | Kobayashi M, Nishita M, Mishima T, Ohashi K, Mizuno K. |
| タイトル | MAPKAPK-2-mediated LIM-kinase activation is critical for VEGF-induced actin remodeling and cell migration. |
| ジャーナル | EMBO J |
| Abstract |
Vascular endothelial growth factor-A (VEGF-A) induces actin reorganization and migration of endothelial cells through a p38 mitogen-activated protein kinase (MAPK) pathway. LIM-kinase 1 (LIMK1) induces actin remodeling by phosphorylating and inactivating cofilin, an actin-depolymerizing factor. In this study, we demonstrate that activation of LIMK1 by MAPKAPK-2 (MK2; a downstream kinase of p38 MAPK) represents a novel signaling pathway in VEGF-A-induced cell migration. VEGF-A induced LIMK1 activation and cofilin phosphorylation, and this was inhibited by the p38 MAPK inhibitor SB203580. Although p38 phosphorylated LIMK1 at Ser-310, it failed to activate LIMK1 directly; however, MK2 activated LIMK1 by phosphorylation at Ser-323. Expression of a Ser-323-non-phosphorylatable mutant of LIMK1 suppressed VEGF-A-induced stress fiber formation and cell migration; however, expression of a Ser-323-phosphorylation-mimic mutant enhanced these processes. Knockdown of MK2 by siRNA suppressed VEGF-A-induced LIMK1 activation, stress fiber formation, and cell migration. Expression of kinase-dead LIMK1 suppressed VEGF-A-induced tubule formation. These findings suggest that MK2-mediated LIMK1 phosphorylation/activation plays an essential role in VEGF-A-induced actin reorganization, migration, and tubule formation of endothelial cells. |
| 巻・号 | 25(4) |
| ページ | 713-26 |
| 公開日 | 2006-2-22 |
| DOI | 10.1038/sj.emboj.7600973 |
| PII | 7600973 |
| PMID | 16456544 |
| PMC | PMC1383554 |
| MeSH | Actins / metabolism Amino Acid Substitution Cell Movement / drug effects Cell Movement / physiology* Cofilin 1 / metabolism Endothelial Cells / cytology Endothelial Cells / enzymology* Enzyme Inhibitors / pharmacology Humans Imidazoles / pharmacology Intracellular Signaling Peptides and Proteins Lim Kinases MAP Kinase Signaling System / drug effects MAP Kinase Signaling System / physiology* Mutagenesis, Site-Directed Phosphorylation / drug effects Point Mutation Protein Kinases / genetics Protein Kinases / metabolism Protein Processing, Post-Translational / drug effects Protein Processing, Post-Translational / physiology Protein Serine-Threonine Kinases Pyridines / pharmacology RNA, Small Interfering / genetics Tubulin / metabolism Vascular Endothelial Growth Factor A / metabolism* Vascular Endothelial Growth Factor A / pharmacology p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors p38 Mitogen-Activated Protein Kinases / metabolism |
| IF | 9.889 |
| 引用数 | 109 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | |